Detoxification formation

The liver is the largest glandular organ and its parenchymal cells are called hepatocytes. Liver has numerous functions, including metabolism, detoxification, formation and excretion of bile, storage, and synthesis. Liver diseases include alcohol abuse, medication, chronic hepatitis B and C infections, steatosis and steatohepatitis, autoimmune... 

Detoxifica.tlon. Detoxification systems in the human body often involve reactions that utilize sulfur-containing compounds. For example, reactions in which sulfate esters of potentially toxic compounds are formed, rendering these less toxic or nontoxic, are common as are acetylation reactions involving acetyl—SCoA (45). Another important compound is. Vadenosylmethionine [29908-03-0] (SAM), the active form of methionine. SAM acts as a methylating agent, eg, in detoxification reactions such as the methylation of pyridine derivatives, and in the formation of choline (qv), creatine [60-27-5] carnitine [461-06-3] and epinephrine [329-65-7] (50). 

The metaboHsm of a material may result in the formation of a transformation product of lower intrinsic toxicity than the parent molecule ie, a process of detoxification has occurred. In other cases, the end result is a metaboHte, or metaboHtes, of intrinsically greater toxicity than the parent molecule, ie, metaboHc activation has occurred. Some examples of detoxification and metaboHc-activation processes are given in Table 2. 

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

Drugs and other chemicals such as food additives or insecticides foreign to the body undergo enzymatic transformations that result in loss of pharmacological activity detoxification), or lead to the formation of metabolites with therapeutic or toxic effects bioactivation). 

Noncyanogenic fungi can degrade cyanide to formamide followed by hydrolysis by a hydratase to formate and ammonia (Dumestre et al. 1997). This pathway is also used by some bacteria (Jandyala et al. 2003). Bacteria also use a number of reactions for the detoxification of cyanide, including monooxygenation to COj and ammonia (Wang et al. 1996). 

There are a number of different mechanisms by which microorganisms resist metal toxicity (Table 11.1). Five mechanisms that microbes use to mediate metal toxicity have been proposed and they include (1) formation of a permeability barrier,21-24 (2) active transport,25-29 (3) sequestration,30-32 (4) enzymatic detoxification,33 34 and (5) reduction in sensitivity.35,36 Microbes may use one or more of these mechanisms to exclude nonessential metals and regulate internal concentrations of essential metals. 

Polymerization is the formation of large molecules (polymers) by the bonding together of many smaller molecules. For example, styrene polymerizes to form polystyrene. Polymerization can enhance the tendency of a substance to be adsorbed on mineral surfaces by increasing the molecular weight, but is not likely to result in detoxification of hazardous wastes. 

Methylphenanthrene fulfills the structural requirements but, as in the case of the other monomethylphenanthracenes, is inactive as a tumor initiator on mouse skin ( 5). This seems to be due to facile metabolic detoxification by formation of the 9,10-dihydrodiol, a process which is blocked in the tumorigenic isomers 1,4- and 4,10-dime thy lphenanthrene ( 5,j>). Among the methylated benzoicIphenan-threnes, the 3-,4-,5-, and 6-methyl isomers are the most tumori-genic The 1-methyl isomer, in which the methyl group is present in a 4-sided "fjord , is only weakly active like the parent hydrocarbon (23). 

The role of N-sulfonyloxy arylamines as ultimate carcinogens appears to be limited. For N-hydroxy-2-naphthylamine, conversion by rat hepatic sulfotransferase to a N-sulfonyloxy metabolite results primarily in decomposition to 2-amino-l-naphthol and 1-sulfonyloxy-2-naphthylamine which are also major urinary metabolites and reaction with added nucleophiles is very low, which suggests an overall detoxification process (9,17). However, for 4-aminoazobenzene and N-hydroxy-AAF, which are potent hepatocarcinogens in the newborn mouse, evidence has been presented that strongly implicates their N-sulfonyloxy arylamine esters as ultimate hepatocarcinogens in this species (10,104). This includes the inhibition of arylamine-DNA adduct formation and tumorigenesis by the sulfotransferase inhibitor pentachlorophenol, the reduced tumor incidence in brachymorphic mice that are deficient in PAPS biosynthesis (10,115), and the relatively low O-acetyltransferase activity of mouse liver for N-hydroxy-4-aminoazobenzene and N-OH-AF (7,114,115). 

As pointed out earlier a third class of B12-dependent enzymes, present in anaerobic microbes, carry out reductive dehalogenation reactions, which play an important role in the detoxification of chlorinated aliphatic and aromatic compounds, among which are many important man-made pollutants. The role of B12 in this class of enzymes is not clear— possibly by formation of an organocobalt adduct, as in the case of methyltransferases or alternatively by the corrinoid serving as an electron donor. 

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